Lane J S, Todd K E, Lewis M P, Gloor B, Ashley S W, Reber H A, McFadden D W, Chandler C F
Department of Surgery, UCLA Medical Center 90095, USA.
Surgery. 1997 Aug;122(2):288-94. doi: 10.1016/s0039-6060(97)90020-9.
Intestinal ischemia/reperfusion (I/R) is known to increase systemic cytokine levels, as well as to activate neutrophils in distant organs. This study was designed to investigate the effect of interleukin-10 (IL-10) on cytokine release, pulmonary neutrophil accumulation, and histologic changes in a murine model of I/R.
Forty female Swiss-Webster mice were divided into four groups. Group 1 underwent 45 minutes of superior mesenteric artery occlusion followed by 3-hour reperfusion (I/R). Group 2 underwent laparotomy alone (Sham). Group 3 underwent I/R, but was treated with IL-10, 10,000 units IP every 2 hours, starting 1 hour before reperfusion (Pretreatment). Group 4 was treated with an equal dose of IL-10, starting 1 hour after reperfusion (Posttreatment). All animals were killed at 3 hours, standard assays were performed for serum cytokine levels, and lung myeloperoxidase activity and intestinal histology were scored.
Serum cytokines (TNF-alpha and IL-6), lung myeloperoxidase levels, and histologic score were significantly reduced when IL-10 was administered either before or after reperfusion.
IL-10 reduced the severity of local and systemic inflammation in a murine model of intestinal I/R when given before or after reperfusion injury. These observations suggest that IL-10 may exert its effect by blocking cytokine production and distant organ neutrophil accumulation.
已知肠道缺血/再灌注(I/R)会增加全身细胞因子水平,并激活远处器官中的中性粒细胞。本研究旨在探讨白细胞介素-10(IL-10)对I/R小鼠模型中细胞因子释放、肺中性粒细胞聚集和组织学变化的影响。
将40只雌性瑞士-韦伯斯特小鼠分为四组。第1组进行45分钟的肠系膜上动脉闭塞,随后进行3小时再灌注(I/R)。第2组仅进行剖腹手术(假手术)。第3组进行I/R,但在再灌注前1小时开始每2小时腹腔注射10000单位IL-10进行治疗(预处理)。第4组在再灌注后1小时开始用等量剂量的IL-10进行治疗(后处理)。所有动物在3小时时处死,进行血清细胞因子水平的标准检测,并对肺髓过氧化物酶活性和肠道组织学进行评分。
在再灌注前或后给予IL-10时,血清细胞因子(TNF-α和IL-6)、肺髓过氧化物酶水平和组织学评分均显著降低。
在再灌注损伤前或后给予IL-10可减轻小鼠肠道I/R模型中局部和全身炎症的严重程度。这些观察结果表明,IL-10可能通过阻断细胞因子产生和远处器官中性粒细胞聚集发挥其作用。